H2S prevents the disruption of the blood-brain barrier in rats with prenatal hyperhomocysteinemia.

Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of H2S donors -NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of dl-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or H2S donors. Rats with hHCY demonstrated high levels of NO metabolite - nitrites and proinflammatory cytokines (IL-1ß, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that H2S has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.

Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats.

AIMS: Neonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine - hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy. MAIN METHODS: Prenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed. KEY FINDINGS: Rats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats. SIGNIFICANCE: The higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.

Heart failure with preserved left ventricular ejection fraction in patients with obstructive sleep apnea syndrome: prognostic value of biomarkers.

Aim      To study the role of soluble ST2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), and С-reactive protein (CRP) in patients with chronic heart failure and preserved left ventricular ejection fraction (CHF with pLVEF) and syndrome of obstructive sleep apnea (SOSA) in stratification of the risk for development of cardiovascular complications (CVC) during one month of a prospective observation.Material and methods  The study included 71 men with SOSA with an apnea/hypopnea index (AHI) >15 per hour, abdominal obesity, and arterial hypertension. Polysomnographic study and echocardiography according to a standard protocol with additional evaluation of left ventricular myocardial fractional changes and work index were performed for all patients at baseline and after 12 months of observation. Serum concentrations of sST2 , NT-proBNP, and CRP were measured at baseline by enzyme-linked immunoassay (ELISA).Results The ROC analysis showed that the cutoff point characterizing the development of CVC were sST2 concentrations ≥29.67 ng/l (area under the curve, AUC, 0.773, sensitivity 65.71 %, specificity 86.11 %; p<0.0001) while concentrations of NT-proBNP (AUC 0.619; p=0.081) and CRP (AUC 0.511; р=0.869) were not prognostic markers for the risk of CVC. According to data of the ROC analysis, all patients were divided into 2 groups based on the sST2 cutoff point: group 1 included 29 patients with ST2 ≥29.67 ng/l and group 2 included 42 patients with ST2 <29.67 ng/l. The Kaplan-Meyer analysis showed that the incidence of CVC was higher in group 1 than in group 2 (79.3 and 28.6 %, respectively, p<0.001). The regression analysis showed that adding values of AHI and left ventricular myocardial mass index (LVMMI) to sST2 in the model increased the analysis predictive significance.Conclusion      Measuring sST2 concentration may be used as a noninvasive marker for assessment of the risk of CVC development in patients with CHF with pLVEF and SOSA within 12 months of observation. Adding AHI and LVMMI values to the model increases the predictive significance of the analysis.

Reinforcement of Epoxy Composites with Graphite-Graphene Structures.

As a result of the research, the possibility of directional control of the operational properties of epoxy composites by the use of small additives of thermally expanded graphite-graphene structures has been proved. The rational content of the structuring additive in the composition of the epoxy composite (0.05 parts by mass.) was selected, which ensured an increase in the studied complex of physico-mechanical properties. The influence of thermally expanded graphite on the process of structure formation of an epoxy composite has been established. The addition of thermally expanded graphite increases thermal, fire and heat resistance as well as the coefficient of heat-conducting epoxy composite.

Ultrastructural Analysis of Urethral Polyps against the Background of Urogenital Infection.

We performed an electron microscopic study of samples of urethral polyps obtained from 90 women (mean age 52.5±4.9 years). According to PCR and culture studies, the most common infectious agent in patients with urethral polyps is U. urealyticum (100% cases). In 70% cases, this infectious agent was present as monoinfection, of these, clinically significant concentration (>106 CFU/ml) were found in 53.3% cases. In 30% cases, associations with C. trachomatis, T. vaginalis, and M. genitalium were found. We observed significant ultrastructural heterogeneity of the epithelial cells in urethral polyps, which manifested in a combination of hyperplastic and metaplastic changes and signs of cytodestruction. Detection of mycoplasma-like bodies in connective tissue mononuclear cells and viral particles in epithelial cells during ultrastructural study, including cases with negative PCR results, indicates the pathogenetic role of latent infection in the formation of urethral polyps.

Side projections of double-helical DNA: example of binding patterns of DNA in the complex with factor TFIIIA.

Communicated by Ramaswamy H. Sarma.

Hydrogen Sulfide Ameliorates Developmental Impairments of Rat Offspring with Prenatal Hyperhomocysteinemia.

Maternal high levels of the redox active amino acid homocysteine-called hyperhomocysteinemia (hHCY)-can affect the health state of the progeny. The effects of hydrogen sulfide (H2S) treatment on rats with maternal hHCY remain unknown. In the present study, we characterized the physical development, reflex ontogeny, locomotion and exploratory activity, muscle strength, motor coordination, and brain redox state of pups with maternal hHCY and tested potential beneficial action of the H2S donor-sodium hydrosulfide (NaHS)-on these parameters. Our results indicate a significant decrease in litter size and body weight of pups from dams fed with methionine-rich diet. In hHCY pups, a delay in the formation of sensory-motor reflexes was observed. Locomotor activity tested in the open field by head rearings, crossed squares, and rearings of hHCY pups at all studied ages (P8, P16, and P26) was diminished. Exploratory activity was decreased, and emotionality was higher in rats with hHCY. Prenatal hHCY resulted in reduced muscle strength and motor coordination assessed by the paw grip endurance test and rotarod test. Remarkably, administration of NaHS to pregnant rats with hHCY prevented the observed deleterious effects of high homocysteine on fetus development. In rats with prenatal hHCY, the endogenous generation of H2S brain tissues was lower compared to control and NaHS administration restored the H2S level to control values. Moreover, using redox signaling assays, we found an increased level of malondialdehyde (MDA), the end product of lipid peroxidation, and decreased activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the brain tissues of rats of the hHCY group. Notably, NaHS treatment restored the level of MDA and the activity of SOD and GPx. Our data suggest that H2S has neuroprotective/antioxidant effects against homocysteine-induced neurotoxicity providing a potential strategy for the prevention of developmental impairments in newborns.

Universal sensor based on the spectroscopy of glow discharge for the detection of traces of atoms or molecules in air.

A sensitive and versatile sensor for the detection of traces of atoms or molecules in air based on the emission spectroscopy of glow discharge in air has been developed and studied. The advantages of this sensor compared to other well-known methods are that it renders the use of ultrahigh vacuum or cryogenic temperatures superfluous. The sensor is insensitive to the presence of water vapor (for example, in exhaled air) because of the absence of strong water lines in the visible spectral range. It has a high spectral selectivity limited only by Doppler broadening of the emission lines. The high selectivity of the sensor combined with a wide spectral range allows the detection of many toxic impurities, which can be present in air. Moreover, the spectral range used covers almost all biomarkers in exhaled air, making the proposed sensor extremely interesting for medical applications. To our knowledge, the proposed method is the first based on a glow discharge in air.

Pathomorphological Analysis and Evaluation of Microcirculation in Polyps of the External Urethral Meatus in Women.

Combinations of various factors of polypogenesis determine the formation of a mixed structural phenotype of urethral polyps consisting of heterogeneous changes of the epithelium (hyperplasia, metaplasia, and erosions), inflammatory cell infiltration of the stroma, and dilatation of the venous plexus vessels. Urogenital infections are associated with the predominance of symptoms of inflammation, high serum levels of IL-1ß and TNF-α, more extensive areas of inflammatory infiltration and subepithelial microvascular bed, predominance of hyperemic form of microcirculatory disorders. The combination of hyperplastic reactions of the epithelial layer with neoangiogenesis and myofibroblast proliferation in the subepithelial zone confirms the key role of dysregeneratory hyperplasia in the mechanisms of polypogenesis.

The effects of exogenous nitric oxide on the function of neuromuscular synapses.

Extracellular recording experiments using neuromuscular skin/chest muscle preparations from lake frogs were performed at low extracellular Ca2+ ion concentrations to study the effect of L-arginine (the substrate for nitric oxide synthesis) and N(G)-nitro-L-arginine methyl ester (a blocker of NO synthase) on the parameters of evoked transmitter secretion and ion currents in motor nerve endings. L-arginine at a concentration of 100 microM decreased the amplitude of endplate currents as well as their quantum composition, and also increased the amplitude of the third phase of the evoked nerve ending response, which reflects the kinetics of potassium influx currents. N(G)-nitro-L-arginine methyl ester at a condition of 100 microM led to increases in the amplitude and quantum composition of endplate currents and decreased the amplitude of the third phase of the evoked nerve ending response. It is suggested that endogenous nitric oxide is produced in frog neuromuscular synapses, which in normal conditions suppresses transmitter secretion and modulates the function of potassium channels in the nerve ending.

Structure of the O-specific polysaccharide chain of Shigella boydii type 5 lipopolysaccharide: a repeated study.

An acidic, partially O-acetylated O-specific polysaccharide was obtained by mild acid degradation of Shigella boydii type 5 lipopolysaccharide and studied by 1H and 13C NMR spectroscopy, including 2D COSY, 13C-1H heteronuclear COSY, 1D NOE, and 2D ROESY experiments, and chemical methods (sugar and methylation analysis, O-deacetylation, carboxyl reduction, solvolysis with anhydrous HF, partial acid hydrolysis. Smith degradation). It was concluded that the polysaccharide has a hexasaccharide repeating unit of the following structure: [Formula: See Text] with the degree of O-acetylation varying over 30-50%. The established structure differs from that proposed recently for the O-specific polysaccharide of the same S. boydii serotype [M.J. Albert et al., Carbohydr. Res., 265 (1994) 121-127].